Naviaux et. al.: Metabolic features of chronic fatigue syndrome

[Simon]

Or can we say that Hanson replicated at least part of Naviaux´s study?

That's fair. But both are fairly small studies and we haven't seen the detail of the Hanson paper so it's hard to say much more for now.

Did the Hanson team test for sphingolipids?

Yes, and found no significant differences (see left hand column).

 

[Sidereal]

Yes, I'm a bit hazy on this, but I think Q<0.15 means a false discovery rate of 15% i.e. 15% (1 in 7) of the reported "abnormalities" would be expected to be a false positive (that's NOT the same as p<0.15, which would be much slacker and bring in a lot of false positives).

That's correct, the figure in the slide is a q value not a p value.

I'm a bit fuzzy on the significance threshold in the Naviaux paper. Here is what the stats section says:

Data Analysis. Metabolomic data were log-transformed, scaled by control SDs,
and analyzed by multivariate PLSDA, PCA, t test, univariate ANOVA with
pairwise comparisons, and post hoc correction for multiple hypothesis testing
using Fisher’s least significant difference method in MetaboAnalyst (56),
or the FDR method of Benjamini and Hochberg (57). Metabolites with variable
importance in projection (VIP) scores determined by PLSDA that were
greater than 1.5 were considered significant.

FDR method = false discovery rate

https://en.wikipedia.org/wiki/False_discovery_rate

I think the details will change as this is repeated in larger, more diverse cohorts, but I doubt that the core finding of a hypometabolic state will be refuted.

 

[Snow Leopard]

For those asking about the full list of what was investigated, it will be forthcoming on this link:

http://metabolomicsworkbench.org/data/DRCCMetadata.php?Mode=Study&StudyID=ST000450

From the footnote on the paper:
Data deposition: The data reported in this paper have been deposited in the NIH Metabolomics Data Repository and Coordinating Center (DRCC) (accession no. ST000450).

 

[aimossy]

Thanks so much @Snow Leopard

 

[Marco]

Yes, I'm a bit hazy on this, but I think Q<0.15 means a false discovery rate of 15% i.e. 15% (1 in 7) of the reported "abnormalities" would be expected to be a false positive (that's NOT the same as p<0.15, which would be much slacker and bring in a lot of false positives). The previous slide showed Q<0.10 was used by Naviaux in his study. I need to spend more fun time on these stats.

I'm not sure about that Simon. I'm pretty sure that a p value of 0.15 does mean that there's a 15% likelihood that it's due to chance.

I wasn't familiar with q values but it looks like they're used to correct the p value for multiple comparisons and result in a marginally less stringent level of confidence than the p value :

http://www.science.smith.edu/cmbs/wp-content/uploads/sites/36/2015/09/P-and-q-values-in-RNA-Seq.pdf

So - thanks - I've learned something

 

[Advocate]

...not only does Cpn cause 'Chronic Fatigue'

I've read your post several times, understanding a little more each time, but please, sir, what is "Cpn?" Thanks.

.

 

[Hutan]

Did the Hanson team test for sphingolipids?

Yes, and found no significant differences (see left hand column).

@Simon, are you referring to the comparison table? Yes, the left hand column shows that Naviaux found significant differences in sphingolipids. The fact that it isn't in the central column means that the Hanson team did not also find differences in sphingolipids. But we don't know why they didn't find differences and one possibility is that they didn't test for them.

Probably the Hanson team did test sphingolipids and found no difference, but, unless I am missing something, this table alone can't tell us that. I look forward to finding out if they were tested and, if they were, if the different testing methods of both teams might have affected their findings on this particular metabolite.

(It was encouraging to hear that the two teams had used quite different testing methods and yet still found many similar results. I'd like to understand the testing methods a bit more.)

 

[cigana]

Phospholipids seem to be a common problem. I had McClaren's tests done a few years back which showed damaged cell membranes and underwent IV lipid replacement over a number of months. That corrected the damage, but I saw no improvement in symptoms.
So this may be evidence that simply replacing the low metabolites is not the way treat the problem, but rather to find out how to modify the signalling problems.
(More evidence for this from the fact that I do find immediate, drammatic symptom relief from strong anti inflammatories).

 

[Gingergrrl]

but please, sir, what is "Cpn?"

I didn't see the original reference but usually this refers to Chlamydia Pneumoniae (which I am most likely spelling incorrectly)!

 

[knackers323]

@cigana what anti inflammatorys have worked?

 

[cigana]

@cigana what anti inflammatorys have worked?

Gc-MAF, ibuprofen and high dose amoxycillin (<- I'm fairly confident it's the anti-inflammatory component that does the trick).
Like many others, I also feel incredibly improved in certain "clean" locations around the world, which suggests I'm reacting to some environmental stressor.

 

[JaimeS]

Gc-MAF, ibuprofen and high dose amoxycillin (<- I'm fairly confident it's the anti-inflammatory component that does the trick).
Like many others, I also feel incredibly improved in certain "clean" locations around the world, which suggests I'm reacting to some environmental stressor.

Aleve works when I'm getting inflammatory symptoms.

I don't know what to make of the fact that apparently downtown Baltimore is a more 'pristine' environment than I'm living in right now....

 

[actup]

*nodnod*

But ppl have discovered them now in other places, such as T-cells. They may end up being part of other cell types as well.

@JaimeS, sorry if this is the wrong place to post kudos for your 08/30 article on Naviaux's paper @#MEAction. I have to say I was thoroughly blown away by your brilliant and perfectly detailed (zero exaggeration in my use of adjectives) article. Very few science journalists can make such complex ideas so understandable and entertaining at the same time. Brava!

 

[luminescencs]

These mutations show that the latent ability to enter into a hypometabolic state during times of environmental threat is adaptive, even though it comes at the cost of decreasing the optimal functional capacity. Similar to dauer, CFS appears to represent a hypometabolic survival state that is triggered by environmental stress. The metabolic features of CFS and dauer correspond to the same pathways that characterize the acute CDR and metabolic syndrome (50) but are regulated in the opposite direction. For example, cholesterol, phospholipids, and uric acid are often elevated in the acute CDR and metabolic syndrome, but these metabolites were decreased in CFS patients.

Interesting article. And we know some of us are more vulnerable/prone to various stressors.

 

[FMMM1]

I've only scanned the paper (and I haven't read the previous comments) but, in terms of diagnostic testing, this is deliverable. The Government laboratories here in the UK get approximately £200 ($270) for a statutory LC-MS test [i.e. European Union food testing programs]; metabolomics instruments are basically an LC-MS/MS with a piece of fancy software (to interpret the signal).

This test needs to be tested on a larger sample group (try Vicky Whittemore) or your local government to deliver this.

Also, what's keeping the switch turned on, i.e. maintaining the hypometabolic state, is it a dodgy sensor or an underlying trigger (threat e.g. virus)? Again, try Vicky Whittemore or your Government to deliver this research.

If your in the UK where does this leave PACE, in the dustbin perhaps since its difficult to see how CBT etc could correct underlying metabolic issues. Ask you local politician for their views via a public forum (e.g. online).

This is good news, even if the benefits may take some time. Well done to those involved.

 

[Sidereal]

What would be freakin' awesome is if someone did a metabolomics study pre and post exercise challenge, showing objective abnormalities (metabolism crashing even further) during the PEM state, say 24-48 hrs after exertion. This sort of study would be the stuff of nightmares for CBT/GET pushers.

 

[JaimeS]

If your in the UK where does this leave PACE, in the dustbin perhaps since its difficult to see how CBT etc could correct underlying metabolic issues.

They will find a way.

As illnesses previously thought to be due to the will -- fixable with a bit of talk therapy, or not fixable at all -- are more and more becoming the purview of medical specialists, now that we understand they are in fact due to:

• Genetics, and somewhat treatable
• Hormone imbalances, and definitively treatable
• Pathogens, and somewhat treatable

...people who utilize the BPS model are now aiming in reverse. Studies are coming out every day on "depression in cancer" and "CBT for MS". The bit where you acknowledge it's a real disease inhibits this theory not a whit. If you are of the opinion (or at any rate, your pocketbook is of the opinion) that mentality has a strong effect on illness, you can peddle that idea anyplace.

We've made the swing from biomedical research and treatments squeezing their way into the psychogenic realm to the psychogenic realm squeezing its way into biomedical research.

@Sidereal that would absolutely be the final domino. We need this to happen, stat! As a milder patient I would agree to this even if it would crash me. For the good of the community!

*raises sword and shield*

-J

 

[JaimeS]

Wow, @actup ... thank you!

 

[Bob]

I've just noticed that the forum has emojis for dauer worm larvae!

I had wondered if they were there for a purpose!

 

[Hutan]

What would be freakin' awesome is if someone did a metabolomics study pre and post exercise challenge, showing objective abnormalities (metabolism crashing even further) during the PEM state, say 24-48 hrs after exertion. This sort of study would be the stuff of nightmares for CBT/GET pushers.

Yes, that would be freakin' awesome.

They will find a way.

But yes, the BPS crowd will find a way to GET around such a finding. In the same way as they dismiss pain and other symptom exacerbations as things to be pushed through (no pain, no gain), they will dismiss the underlying metabolic changes. They will stress the graded nature of GET. You see it's our fault that we take a boom and bust approach to activity - our minds are faulty and so we need the guidance of a medically qualified someone to tell us exactly how much exercise to do each day.